PMID- 22766232
OWN - NLM
STAT- MEDLINE
DCOM- 20130123
LR  - 20131121
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 221
DP  - 2012 Sep 27
TI  - Strong neuroprotection with a novel platinum nanoparticle against ischemic 
      stroke- and tissue plasminogen activator-related brain damages in mice.
PG  - 47-55
LID - 10.1016/j.neuroscience.2012.06.060 [doi]
AB  - Reactive oxygen species (ROS) are major exacerbation factor in acute ischemic 
      stroke, and thrombolytic agent tissue plasminogen activator (tPA) may worsen 
      motor function and cerebral infarcts. The platinum nanoparticle (nPt) is a novel 
      ROS scavenger, and thus we examined the clinical and neuroprotective effects of 
      nPt in ischemic mouse brains. Mice were subjected to transient middle cerebral 
      artery occlusion (tMCAO) for 60 min and divided into the following four groups by 
      intravenous administration upon reperfusion, vehicle, tPA, tPA+nPt, and nPt. At 
      48 h after tMCAO, motor function, infarct volume, immunohistochemical analyses of 
      neurovascular unit (NVU), in vivo imaging of matrix metalloproteinase (MMP), and 
      zymography for MMP-9 activity were examined. Superoxide anion generation at 2h 
      after tMCAO was also examined with hydroethidine (HEt). As a result, 
      administration of tPA deteriorated the motor function and infarct volume as 
      compared to vehicle. In vivo optical imaging of MMP showed strong fluorescent 
      signals in affected regions of tMCAO groups. Immunohistochemical analyses 
      revealed that tMCAO resulted in a minimal decrease of NAGO and occludin, but a 
      great decrease of collagen IV and a remarkable increase of MMP-9. HEt stain 
      showed increased ROS generation by tMCAO. All these results became pronounced 
      with tPA administration, and were greatly reduced by nPt. The present study 
      demonstrates that nPt treatment ameliorates neurological function and brain 
      damage in acute cerebral infarction with neuroprotective effect on NVU and 
      inactivation of MMP-9. The strong reduction of ROS production by nPt could 
      account for these remarkable neurological and neuroprotective effects against 
      ischemic stroke.
CI  - Copyright (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Takamiya, M
AU  - Takamiya M
AD  - Department of Neurology, Okayama University Graduate School of Medicine, 
      Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan. 
      motonori@cc.okayama-u.ac.jp
FAU - Miyamoto, Y
AU  - Miyamoto Y
FAU - Yamashita, T
AU  - Yamashita T
FAU - Deguchi, K
AU  - Deguchi K
FAU - Ohta, Y
AU  - Ohta Y
FAU - Abe, K
AU  - Abe K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120703
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Collagen Type IV)
RN  - 0 (Phenanthridines)
RN  - 0 (Reactive Oxygen Species)
RN  - 11062-77-4 (Superoxides)
RN  - 38483-26-0 (hydroethidine)
RN  - 49DFR088MY (Platinum)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Brain Infarction/*chemically induced/*prevention & control
MH  - Collagen Type IV/metabolism
MH  - Disease Models, Animal
MH  - Drug Administration Schedule
MH  - Infarction, Middle Cerebral Artery/*drug therapy
MH  - Laser-Doppler Flowmetry
MH  - Male
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Metal Nanoparticles/*therapeutic use
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Movement Disorders/etiology/prevention & control
MH  - Phenanthridines/metabolism
MH  - Platinum/*therapeutic use
MH  - Reactive Oxygen Species/metabolism
MH  - Regional Blood Flow/drug effects
MH  - Reperfusion
MH  - Spectroscopy, Near-Infrared
MH  - Superoxides/metabolism
MH  - Time Factors
MH  - Tissue Plasminogen Activator/*adverse effects
EDAT- 2012/07/07 06:00
MHDA- 2013/01/24 06:00
CRDT- 2012/07/07 06:00
PHST- 2012/05/02 00:00 [received]
PHST- 2012/06/24 00:00 [revised]
PHST- 2012/06/25 00:00 [accepted]
PHST- 2012/07/07 06:00 [entrez]
PHST- 2012/07/07 06:00 [pubmed]
PHST- 2013/01/24 06:00 [medline]
AID - S0306-4522(12)00678-1 [pii]
AID - 10.1016/j.neuroscience.2012.06.060 [doi]
PST - ppublish
SO  - Neuroscience. 2012 Sep 27;221:47-55. doi: 10.1016/j.neuroscience.2012.06.060. 
      Epub 2012 Jul 3.